Widespread allele-specific topological domains in the human genome are not confined to imprinted gene clusters

Richer, S; Tian, Y; Schoenfelder, S; Hurst, L; Murrell, A; Pisignano, G

Journal article

Widespread allele-specific topological domains in the human genome are not confined to imprinted gene clusters

Abstract:: Abstract Background There is widespread interest in the three-dimensional chromatin conformation of the genome and its impact on gene expression. However, these studies frequently do not consider parent-of-origin differences, such as genomic imprinting, which result in monoallelic expression. In addition, genome-wide allele-specific chromatin conformation associations have not been extensively explored. There are few accessible bioinformatic workflows for investigating allelic conformation differences and these require pre-phased haplotypes which are not widely available. Results We developed a bioinformatic pipeline, “HiCFlow,” that performs haplotype assembly and visualization of parental chromatin architecture. We benchmarked the pipeline using prototype haplotype phased Hi-C data from GM12878 cells at three disease-associated imprinted gene clusters. Using Region Capture Hi-C and Hi-C data from human cell lines (1-7HB2, IMR-90, and H1-hESCs), we can robustly identify the known stable allele-specific interactions at the IGF2-H19 locus. Other imprinted loci (DLK1 and SNRPN) are more variable and there is no “canonical imprinted 3D structure,” but we could detect allele-specific differences in A/B compartmentalization. Genome-wide, when topologically associating domains (TADs) are unbiasedly ranked according to their allele-specific contact frequencies, a set of allele-specific TADs could be defined. These occur in genomic regions of high sequence variation. In addition to imprinted genes, allele-specific TADs are also enriched for allele-specific expressed genes. We find loci that have not previously been identified as allele-specific expressed genes such as the bitter taste receptors (TAS2Rs). Conclusions This study highlights the widespread differences in chromatin conformation between heterozygous loci and provides a new framework for understanding allele-specific expressed genes.

Publication status:: Published

Peer review status:: Peer reviewed

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APA Style

Richer, S., Tian, Y., Schoenfelder, S., Hurst, L., Murrell, A., & Pisignano, G. (2023). Widespread allele-specific topological domains in the human genome are not confined to imprinted gene clusters. Genome Biology, 24(1), 40–40.

MLA Style

Richer, S, et al. “Widespread Allele-Specific Topological Domains in the Human Genome Are Not Confined to Imprinted Gene Clusters.” Genome Biology, vol. 24, no. 1, 2023, pp. 40–40.

Chicago Style

Richer, S, Y Tian, S Schoenfelder, L Hurst, A Murrell, and G Pisignano. 2023. “Widespread Allele-Specific Topological Domains in the Human Genome Are Not Confined to Imprinted Gene Clusters.” Genome Biology 24 (1): 40–40.
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